People who have macular degeneration often lose the ability to see in the part of vision normally used for daily tasks such as reading and recognizing faces. This often debilitating loss is expected to afflict 3 million US citizens by 202. An essential health-related goal is therefore to develop strategies that allow patients with macular degeneration to make better use of their spared peripheral vision. Despite loss of central vision, many patients learn to successfully navigate the world, becoming adept at using peripheral vision for tasks normally done with central vision. The mechanisms underlying this visual plasticity are not known, but are of great clinical interest, because better understanding can lead to improved treatment strategies following vision loss. Plasticity after macular degeneration is also of great basic science interest because it provides insight to nervous system plasticity in a human model, which is key for understanding and treating a host of neurological and psychiatric disorders. Most work examining plasticity after vision loss has studied bottom-up remapping of inputs, and this remapping appears to be minimal in adults. We propose to examine connections between the early visual cortex and frontal and parietal brain networks, which have the potential to be more plastic. We will make use of the Human Connectome Project dataset and protocols to identify how the structure and connections of early visual areas are altered following loss of central vision due to macular degeneration. The overall objective of this proposal is to identify the neuroplastic mechanisms that allow patients with MD to use peripheral vision for tasks, such as reading and recognizing faces, for which people with healthy vision use the macula. Our central hypothesis is that greater reliance on peripheral vision following MD leads visual cortical regions representing the periphery to become structurally and functionally more similar to those representing the macula, thus improving functional vision. The motivation for the proposed research is that better understanding of neural mechanisms that underlie enhanced peripheral vision in patients who suffer from macular degeneration is essential to developing the next generation of therapeutic interventions. We will test our central hypothesis by identifying how the following characteristics of early visual areas change after central vision loss: 1) functional connectivity to fronto-parietal control regions, (2 structural measures of white matter integrity, (3) cortical thickness. We will compare participants with age-related macular degeneration to matched controls using the Human Connectome Project protocols. These aims are expected to yield information about how top-down connections to early visual areas contribute to plasticity after vision loss. This contribution wil be significant because it will fundamentally alter our understanding of how the brain compensates after vision loss, and revise our understanding of neural plasticity in general. This knowledge wil guide the development of new strategies for training patients with vision loss to use their spared vision more effectively.